Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study addresses the potential effects of pacing-induced myocardial ischemia on the secretion of coagulant and fibrinolytic factors within the coronary circulation. In 6 patients undergoing programmed ventricular stimulation with repeated induction of clinical ventricular tachycardia, the coronary release of tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) capacity, von Willebrand factor antigen (WF:Ag), and prostacyclin (6-keto-PGF 1a) was measured. Blood samples were collected simultaneously from the ascending aorta and the coronary sinus at baseline and immediately after the induction of ventricular tachycardia. The occurrence of pacing-induced myocardial ischemia was established by myocardial net lactate production. Myocardial ischemia was induced in every patient by repeated pacing trials. Pacing-induced ischemia did not affect the coronary release of any of the above factors. Consequently, there was no alteration of transcardiac gradients of thrombin-antithrombin complexes and D-dimer. The present results indicate that pacing-induced myocardial ischemia does not affect the release of coagulant and fibrinolytic endothelial factors or prostacyclin into the coronary circulation.
 ...
PMID:Pacing-induced myocardial ischemia does not affect the endothelial release of coagulant and fibrinolytic factors into the coronary circulation. 170 56

The clinical manifestations of Rocky Mountain spotted fever (RMSF) result from Rickettsia rickettsii (R rickettsii) infection of endothelial cells and are mediated by pathologic changes localized to the vessel, including in situ thrombosis and tissue ischemia. This study uses in vitro infection of cultured human umbilical vein endothelial cells with R rickettsii to test the hypothesis that such infection induces von Willebrand factor (vWF) release from Weibel-Palade bodies, a process that could contribute to thrombotic changes. At 24 hours postinfection, there was an increase in metabolically prelabeled large multimers of vWF in the culture medium, with a concomitant decrease of these forms in the cell lysate samples. This release reaction was specific for the large multimer pool of vWF, localized to Weibel-Palade bodies, because no change in the distribution of dimeric forms between cells and culture medium was detected. Double-label immunofluorescence staining showed an inverse correlation between the number of R rickettsii and the number of Weibel-Palade bodies in infected cells. Cell lysis was minimal at 24 hours postinfection, as no detectable intracellular precursor forms (molecular weight 260,000) of vWF were released into the culture medium, there was no decrease in cell viability as measured by trypan blue exclusion, and no increase in 51Cr-release into the culture medium was observed when compared with uninfected controls. Release was likely a direct effect of the intracellular presence of the organism, rather than due to a noxious soluble factor such as endotoxin, because culture medium conditioned by infected endothelial cells was ineffective at inducing release in uninfected endothelial cell cultures. In summary, in vitro infection of endothelial cells by R rickettsii induces release of Weibel-Palade body contents, a process that may contribute to the pathogenesis of RMSF.
 ...
PMID:Rickettsia rickettsii infection of cultured endothelial cells induces release of large von Willebrand factor multimers from Weibel-Palade bodies. 182 55

The effects of early coronary recanalization on the plasma levels of two procoagulant acute phase proteins, the fastacting plasminogen activator inhibitor and von Willebrand factor, were investigated in 24 patients with myocardial infarction receiving intravenous recombinant tissue-type plasminogen activator (rt-PA) within 6 h of the onset of symptoms. Coronary angiography was performed before and 90 min after the start of rt-PA infusion. Continuous electrocardiographic recordings and 4 h plasma creatine kinase MB isoenzyme (CK MB) were performed over the first 24 h. Plasma plasminogen activator inhibitor activity, von Willebrand factor and C-reactive protein were measured before rt-PA infusion, daily for the first 3 days and after 90 days. In the entire group, plasminogen activator inhibitor activity peaked at 24 h (day 1), representing a significant increase over values at all other times (p = 0.03). von Willebrand factor was higher in the first 2 days of infarction compared with after 90 days (p = 0.001). C-reactive protein peaked on day 2, with an eightfold increase over values on admission (p = 0.001). In the 16 patients with a patent infarct-related artery at 90 min, infarct size estimated by integrated 24 h CK MB, time for ST segment elevation to decrease to half-maximum and peak C-reactive protein were reduced significantly by more than twofold compared with values in the 8 patients with an occluded artery at 90 min. The patients with early recanalization also had lower plasminogen activator inhibitor activity on day 2 (p = 0.05) and day 3 (p = 0.02) and lower 0 to 72 h averaged von Willebrand factor (p = 0.01). Thus, early coronary recanalization curtails the response of plasminogen activator inhibitor activity and von Willebrand factor to myocardial infarction, most likely by reducing the extent of ischemia and necrosis and the consequent acute phase reaction. By blunting the early postinfarction procoagulant state, prompt recanalization may reduce the risk of thromboembolic complications in the first days after myocardial infarction.
 ...
PMID:Early coronary reperfusion blunts the procoagulant response of plasminogen activator inhibitor-1 and von Willebrand factor in acute myocardial infarction. 212 6

To test the hypothesis that plasma contains native constituents capable of impairing microcirculatory flow in zones of acute ischemic tissue damage, we performed 14C-antipyrine autoradiographic blood flow studies in splenectomized dogs subjected to 35 min of cerebrospinal fluid compression ischemia followed by 30 min of recirculation to the neuraxis. The animals were anticoagulated with heparin and were divided into 4 groups by exposure to various measures before induction of ischemia. Groups 1 and 2 served for comparison with the other groups and underwent, respectively, no glass-wool filtration and glass-wool filtration via an arteriovenous shunt. Post-ischemic brain blood flows in Group 1 were low and focal zones of greatly impaired reperfusion were present. In Group 2, post-ischemic brain blood flows were high and focal perfusion impairment did not occur. Group 3 received homologous purified factor VIII/von Willebrand factor protein (F VIII/vWF) after glass-wool filtration but before induction of ischemia; Group 4 received F VIII/vWF-poor cryoprecipitate at the same time point. The purpose of administering the plasma preparations was to check for the presence of activity that nullified the enhancement of post-ischemic reperfusion expected after exposure to glass-wool. The results indicate that activity deleterious to post-ischemic reperfusion primarily resides in the F VIII/vWF fraction of cryoprecipitate. The F VIII/vWF-poor cryoprecipitate infusate, containing 250 to 800-fold more protein than the F VIII/vWF fraction, produced an intermediate reduction of blood flow.
 ...
PMID:Influence of factor VIII/von Willebrand factor protein (F VIII/vWF) and F VIII/vWF-poor cryoprecipitate on post-ischemic microvascular reperfusion in the central nervous system. 678 87

In clinical flap transplantation, ischaemia may alter reinnervation patterns either directly or by affecting angiogenesis. This study presents the effects of ischaemia on innervation in totally denervated, transiently (30 minutes) or prolongedly ischaemic skin flaps studied immunohistochemically with antisera to PGP 9.5, CGRP and VWF. Following transient ischaemia, an increase in PGP-immunoreactive (PGP-IR) and CGRP-IR nerve fibres in distant skin by day 12 was followed by increased innervation in immediately adjacent skin. The latter increase was maintained up to 24 days which allowed near normal innervation at the suture margin and in adjacent flap tissue, 0.5 cm from the margin. There was concomitant reinnervation from the pedicle by day 24. In prolongedly ischaemic flaps, an earlier and more prolonged increase in innervation was seen in the entire surrounding skin, with innervation around the suture line at 24 days resembling that in the transiently ischaemic flaps despite initial complete nerve fibre depletion in this area. Hypertrophic nerve fibre clusters were seen in fibrotic areas overlying the pedicle. Vascular changes were similar in both groups with vascularization preceding reinnervation. There were no significant differences in reinnervation between the transiently and prolongedly ischaemic flaps at 24 days, despite considerable initial variations. Ischaemia, CGRP, mediators of chronic inflammation and epidermal factors appeared to stimulate angiogenesis and reinnervation.
 ...
PMID:Angiogenesis and reinnervation in skin flaps: the effects of ischaemia examined in an animal model. 752 11

Although endothelial cell injury and microcirculatory intravascular clotting have been implicated in the pathophysiology of skin-flap failure and various hematologically active drugs have been used to improve flap survival, the basic underlying pathophysiology has not been documented previously. In this study of venous ischemia in pig flaps, we focus on the accumulation and distribution of platelets and fibrinogen in the flap, on the morphologic changes in the flap microcirculation, and on changes in various coagulation factors in the venous effluent from the flap. Bilateral buttock skin flaps and latissimus dorsi myocutaneous flaps were designed and elevated on 12 pigs. All flaps had a primary ischemic insult (clamp application to the vascular pedicle) of 2 hours, followed by 2 hours of reperfusion, and then one side was subjected to a 6-hour period of secondary venous ischemia (clamp application to the dominant flap vein). In six animals, radioactively labeled autologous platelets and human fibrinogen were injected intravenously half an hour before termination of secondary venous ischemia. Flaps were weighed and counted for radioactivity. Flap biopsies and the buffy coat of venous effluent were processed for electron microscopy. In the other six animals, venous effluent was collected before secondary ischemia, upon immediate reperfusion, and at 4 and 8 hours after termination of secondary ischemia. Venous plasma levels of fibrinogen, von Willebrand factor, and antithrombin III were measured. Platelet and fibrinogen accumulation was increased in flaps with venous stasis when compared with control flaps at both time intervals studied; a twofold increase was seen prior to reperfusion, and a threefold increase was seen following 4 hours of reperfusion. Venous effluent could not be collected from buttock skin flaps because of slow reflow and clotting in the collecting system. In comparing the venous effluent of control flaps with that of venous ischemic latissimus dorsi flaps, hematocrit was significantly elevated. Blood samples collected for analysis of fibrinogen, antithrombin III, and von Willebrand factor could not be analyzed because of postcollection clotting. Electron microscopy showed extravasation of red blood cells and activated platelets, fibrin, and red blood cells in distended and partly disrupted capillaries. The venous ischemia reperfusion injury is associated with thrombosis in the microcirculation and alterations in consumption of coagulation factors. This study gives physiologic support for potential beneficial effects of treatment modalities that aim at counteracting the different components of thrombus formation.
 ...
PMID:Venous ischemia in skin flaps: microcirculatory intravascular thrombosis. 831 29

Although endothelial cell injury and microcirculatory intravascular thrombosis have been implicated in the pathophysiology of skin-flap failure, the basic underlying pathophysiology has not been documented previously. This study focuses on the morphologic changes and the alteration in platelet, fibrinogen, antithrombin III, and von Willebrand factor levels in flaps injured by arterial ischemia and reperfusion. A thrombogenic arterial anastomosis model is compared with simple arterial clamping as methods to achieve flap ischemia. Bilateral buttock skin flaps and latissimus dorsi island flaps were elevated in 12 pigs. All flaps had a primary ischemic insult of 2 hours' duration by simple clamp application. During this interval, a thrombus-generating, microvascular anastomosis was prepared, and during a 2-hour period of reperfusion, laser Doppler and transiluminator monitoring of the vascular pedicle allowed documentation of embolic events from the thrombus-generating anastomosis. In group 1 (n = 6), the flaps were then subjected to 7 (buttock skin) and 5 (latissimus dorsi) hours of complete arterial ischemia by clamping. During the secondary ischemic period, the poor microanastomosis was resected and repaired. Radioactively labeled autologous platelets (111In) and human fibrinogen (125I) were injected intravenously half an hour before secondary reperfusion. After 4 hours of reperfusion, flap biopsies and venous effluent were collected and prepared for electron microscopic analysis. The flaps and control tissue were harvested and the radioactivity was counted. In group 2 (n = 6), flaps were subjected to 6 hours of secondary ischemia by using the same technique as in group 1. Central venous and flap venous blood was sampled at baseline as well as upon immediate secondary reperfusion and after 4 and 8 hours of reperfusion. The hematocrit, platelet count, fibrinogen, antithrombin III, and von Willebrand factor levels were determined for these intervals. Platelets and fibrinogen accumulated significantly in buttock skin flaps and in the latissimus dorsi skin and muscle components as compared with similar control tissue (p < 0.05). There was no significant difference in platelet or fibrinogen accumulation after comparing the two ischemic models. Electron microscopic studies showed occluded capillaries with activated platelets in the flaps. Control tissue showed very little capillary occlusion. Platelet count was significantly decreased both in central venous (p < 0.05) and in adventitial infolding flap venous blood (p < 0.025) during immediate reperfusion as compared with baseline. These findings confirm that microcirculatory intravascular thrombosis is implicated in skin-flap ischemia-reperfusion injury. This study provides physiologic support for treatment modalities aimed at counteracting the various components in the coagulation pathways responsible for thrombus formation.
 ...
PMID:Arterial ischemia in skin flaps: microcirculatory intravascular thrombosis. 831 30

A case of thrombotic microangiopathy presenting as a hemolytic uremic syndrome complicated by untreatable hypertension and ultimately requiring bilateral nephrectomy is discussed. Severe hypertension and renal failure may complicate the course of vascular diseases of the kidney, including thrombotic microangiopathy, chronic hypertension, and scleroderma. Toxins, pressure stress, and immune material may trigger the initial injury to vascular endothelium. The malignant course of these renal vascular diseases seems linked to the severity of vascular injury. Endothelial injury manifests with swelling and detachment of endothelial cells from the basement membrane, expansion of the subendothelial space, and newly formed basement membrane-like material. In arterioles, endothelial injury precedes myointimal swelling and proliferation, leading to vascular lumina narrowing or obliteration and secondary glomerular ischemia, with glomerular tuft collapse and garland-like wrinkling and thickening of the capillary wall. Endothelial cell injury is very likely the common determinant of a cascade of events that lead to irreversible renal failure. When the initial insult (toxins, mechanical stress, antibodies) is promptly removed, lesions are self-limiting and the patient usually recovers. However, a severe insult persisting for some time can lead to chronic and irreversible vascular lesions that, through renal ischemia, trigger maximal activation of the renin angiotensin system with a brisk elevation in arterial blood pressure that may combine to further vascular injury and renal ischemia. Moreover, enhanced shear stress in the severely narrowed microcirculation, through abnormal von Willebrand factor processing, can also favor endothelial injury and platelet aggregation, which may further worsen the vascular lesions and sustain the microangiopathic process. Plasma manipulation, arteriolar vasodilators, and angiotensin-converting enzyme inhibitors normally control the vicious circle, but in few severe cases bilateral nephrectomy remains the last chance to save the patient's life.
 ...
PMID:Malignant vascular disease of the kidney: nature of the lesions, mediators of disease progression, and the case for bilateral nephrectomy. 867 55

This type of thrombotic microangiopathy more commonly resembles the hemolytic-uremic syndrome (HUS) than thrombotic thrombocytopenic purpura (TTP). The syndrome has been associated with the use of cyclosporin, mitomycin C, combinations of other chemotherapeutic and immunosuppressive agents, and total body irradiation. Endothelial cell injury and von Willebrand factor may be involved in pathogenesis of the intravascular platelet aggregation and tissue (especially renal) ischemia and infarction that characterize the entity. The most effective therapy for thrombotic microangiopathy associated with drugs and bone marrow transplantation has not been determined.
 ...
PMID:Thrombotic microangiopathies associated with drugs and bone marrow transplantation. 870 65

Coagulation activation and fibrinolysis parameters were studied in eleven cases of thrombotic microangiopathy concerning eight adult patients. In addition to routine coagulation tests, antithrombin III, von Willebrand factor (vWF), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-dimer (DD), and plasminogen activator inhibitor type 1 (PAI-1) were measured in the plasma at the time of diagnosis and as soon as remission was achieved after therapy with plasma exchange and Iloprost. In the acute phase all patients showed normal aPTT, normal or slightly prolonged prothrombin time, normal or enhanced plasma levels of fibrinogen and antithrombin III, at variance with results in patients affected by disseminated intravascular coagulation. Mean F1+2, TAT, DD, vWF and PAI-1 were elevated in the acute phase, but decreased significantly in the early phase of remission. Our data provide evidence of increased thrombin generation rate which takes place in the acute phase of the disease and does not result in consumption coagulopathy, due to appropriate inhibition by antithrombin III; blood coagulation activation promptly decreased as soon as remission was achieved. Cross-linked fibrin deposition together with PAI-1 may consolidate the platelet plug, eventually resulting in microvascular occlusion and ischemia.
 ...
PMID:Plasmatic parameters of coagulation activation in thrombotic microangiopathy. 895 55


1 2 3 4 5 6 7 8 9 10 Next >>